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Multicenter Study
. 2019 Jul 5;14(7):1056-1066.
doi: 10.2215/CJN.13401118. Epub 2019 Jun 18.

Preformed Donor-Specific HLA Antibodies in Living and Deceased Donor Transplantation: A Multicenter Study

Malte Ziemann  1 , Wolfgang Altermann  2 , Katharina Angert  1 , Wolfgang Arns  3 , Anette Bachmann  4 , Tamam Bakchoul  1 , Bernhard Banas  5 , Annette von Borstel  6 , Klemens Budde  7 , Vanessa Ditt  6 , Gunilla Einecke  8 , Ute Eisenberger  9 , Thorsten Feldkamp  10 , Siegfried Görg  1 , Martina Guthoff  11 , Antje Habicht  12 , Michael Hallensleben  13 , Falko M Heinemann  14 , Nicole Hessler  15 , Christian Hugo  16 , Matthias Kaufmann  17 , Teresa Kauke  18   19   20 , Martina Koch  21 , Inke R König  15 , Christine Kurschat  22 , Claudia Lehmann  23 , Matthias Marget  24 , Anja Mühlfeld  25 , Martin Nitschke  26 , Luiza Pego da Silva  27 , Carmen Quick  16 , Axel Rahmel  28 , Thomas Rath  29 , Petra Reinke  7 , Lutz Renders  30 , Florian Sommer  31 , Bernd Spriewald  32 , Oliver Staeck  7 , Dirk Stippel  33 , Caner Süsal  34 , Bernhard Thiele  35 , Daniel Zecher  5 , Nils Lachmann  36
Affiliations
Multicenter Study

Preformed Donor-Specific HLA Antibodies in Living and Deceased Donor Transplantation: A Multicenter Study

Malte Ziemann et al. Clin J Am Soc Nephrol. .

Abstract

Background and objectives: The prognostic value of preformed donor-specific HLA antibodies (DSA), which are only detectable by sensitive methods, remains controversial for kidney transplantation.

Design, setting, participants, & measurements: The outcome of 4233 consecutive kidney transplants performed between 2012 and 2015 in 18 German transplant centers was evaluated. Most centers used a stepwise pretransplant antibody screening with bead array tests and differentiation of positive samples by single antigen assays. Using these screening results, DSA against HLA-A, -B, -C, -DRB1 and -DQB1 were determined. Data on clinical outcome and possible covariates were collected retrospectively.

Results: Pretransplant DSA were associated with lower overall graft survival, with a hazard ratio of 2.53 for living donation (95% confidence interval [95% CI], 1.49 to 4.29; P<0.001) and 1.59 for deceased donation (95% CI, 1.21 to 2.11; P=0.001). ABO-incompatible transplantation was associated with worse graft survival (hazard ratio, 2.09; 95% CI, 1.33 to 3.27; P=0.001) independent from DSA. There was no difference between DSA against class 1, class 2, or both. Stratification into DSA <3000 medium fluorescence intensity (MFI) and DSA ≥3000 MFI resulted in overlapping survival curves. Therefore, separate analyses were performed for 3-month and long-term graft survival. Although DSA <3000 MFI tended to be associated with both lower 3-month and long-term transplant survival in deceased donation, DSA ≥3000 MFI were only associated with worse long-term transplant survival in deceased donation. In living donation, only strong DSA were associated with reduced graft survival in the first 3 months, but both weak and strong DSA were associated with reduced long-term graft survival. A higher incidence of antibody-mediated rejection within 6 months was only associated with DSA ≥3000 MFI.

Conclusions: Preformed DSA were associated with an increased risk for graft loss in kidney transplantation, which was greater in living than in deceased donation. Even weak DSA <3000 MFI were associated with worse graft survival. This association was stronger in living than deceased donation.

Keywords: ABO-incompatible transplantation; Antibodies; Fluorescence; HLA-A Antigens; Incidence; Prognosis; Retrospective Studies; Tissue Donors; donor-specific HLA antibodies; graft survival; kidney transplantation; preformed HLA antibodies.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
The graft survival of patients with DSA was worse compared with patients without DSA, but not different according to DSA class. Overall graft survival is shown for (A) the total cohort according to the presence of pretransplant DSA, (B) living donors according to the presence of pretransplant DSA, (C) deceased donors according to the presence of pretransplant DSA, (D) the total cohort according to HLA class of pretransplant DSA, (E) living donors according to HLA class of pretransplant DSA, and (F) deceased donors according to HLA class of pretransplant DSA. Numbers of patients at risk are given below the Kaplan–Meier-curves. Log-rank test after exclusion of patients without DSA: (D) P=0.74; (E) P=0.89; (F) P=0.84.
Figure 2.
Figure 2.
Both DSA <3000 MFI and DSA ≥3000 MFI were associated with impaired overall graft survival, while only DSA ≥3000 MFI were associated with early antibody-mediated rejection. Strength of pretransplant DSA are depicted in relation to (A) graft survival for the total cohort, (B) incidence of antibody mediated rejections during the first 6 months after transplantation (*P<0.001 compared with patients without DSA), (C) graft survival for living donors, (D) graft survival for deceased donors, (E) 3-month graft survival for living donors, (F) 3-month graft survival for deceased donors, (G) long-term graft survival starting at the fourth month for living donors, and (H) long-term graft survival starting at the fourth month for deceased donors. Graft survival has not been censored for patient death.
Figure 2.
Figure 2.
Both DSA <3000 MFI and DSA ≥3000 MFI were associated with impaired overall graft survival, while only DSA ≥3000 MFI were associated with early antibody-mediated rejection. Strength of pretransplant DSA are depicted in relation to (A) graft survival for the total cohort, (B) incidence of antibody mediated rejections during the first 6 months after transplantation (*P<0.001 compared with patients without DSA), (C) graft survival for living donors, (D) graft survival for deceased donors, (E) 3-month graft survival for living donors, (F) 3-month graft survival for deceased donors, (G) long-term graft survival starting at the fourth month for living donors, and (H) long-term graft survival starting at the fourth month for deceased donors. Graft survival has not been censored for patient death.
Figure 3.
Figure 3.
ABO-incompatibility was associated with decreased graft and patient survival after living donation. ABO-incompatible living kidney transplantations are compared with ABO-compatible living donations for (A) overall graft survival, (B) patient survival, and (C) death-censored graft survival. GS, graft survival; tx, transplantation.
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